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Study protocol of Phase 2 open-label multicenter randomized controlled trial for granulocyte-colony stimulating factor (GCSF) in post-Kasai Type 3 biliary atresia


Animal studies support RCT findings of improved liver function and short-term benefits using repurposed Granulocyte Colonic Stimulating Factor GCSF in adults with decompensated cirrhosis. We describe the protocol for phase 2 RCT of sequential Kasai-GCSF under an FDA-approved IND to test that GCSF improves early bile flow and post-Kasai biliary atresia BA clinical outcome. Immediate post-Kasai neonates, age 15–180 days, with biopsy-confirmed type 3 BA, without access to early liver transplantation, will be randomized 1:1 to standard of care SOC + GCSF at 10 ug/kg in 3 daily doses within 4 days of Kasai vs SOC + NO-GCSF ( NCT0437391). They will be recruited from children’s hospitals in Vietnam, Pakistan and one US center. The primary objective is to demonstrate that GCSF decreases the proportion of subjects with a 3-month post-Kasai serum Total Bilirubin ≥ 34 umol/L by 20%, (for a = 0.05, b = 0.80, i.e., calculated sample size of 218 subjects). The secondary objectives are to demonstrate that the frequency of post-Kasai cholangitis at 6-month and 24-month transplant-free survival are improved. The benefits are that GCSF is an affordable BA adjunct therapy, especially in developing countries, to improve biliary complications, enhance quality of liver and survival while diminishing costly liver transplantation.

Clinical trial registration: A phase 1 for GCSF dose and safety determination under identifier NCT03395028 was completed in 2019. The current Phase 2 trial was registered under NCT04373941.

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Fig. 1



Biliary atresia


Hematopoietic stem cells


Granulocyte-colony stimulating factor


Cluster of differentiation


Randomized clinical trial


Food and drug administration


Investigational new drug


National clinical trial




Total bilirubin




Gamma glutamyl transpeptidase


White blood cell count


Biliary atresia splenic malformation syndrome


Complete blood count


Liver function test


International normalized ratio


Pediatric end stage liver disease


Cluster of differentiation


Biliary epithelial cell




Common terminology criteria for adverse events


Ductular reaction


Data safety monitoring board


Primary biliary cirrhosis


Primary sclerosing cholangitis


T helper 17


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Funding is provided by Cures Within Reach and by Prometheus USA organizations.

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Correspondence to AiXuan Holterman.

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Nguyen, H.P.A., Ren, J., Butler, M. et al. Study protocol of Phase 2 open-label multicenter randomized controlled trial for granulocyte-colony stimulating factor (GCSF) in post-Kasai Type 3 biliary atresia. Pediatr Surg Int 38, 1019–1030 (2022).

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  • Biliary atresia
  • Kasai, Randomized controlled trial
  • GCSF
  • Low middle income country